Immune response in alcoholics are compromised often putting these individuals at risk for frequent and severe infections. In both humans and mice different subsets of CD4 T helper cells, termed Th1 and Th2, regulate cell-mediated and antibody-mediated immunity, respectively. We previously demonstrated, in a mouse model that closely parallels immune alterations seen in humans, that ethanol consumption polarizes adaptive immune responses, Th1 responses are inhibited and Th2 responses are unaffected or enhanced. We recently made the startling preliminary observation that ethanol consumption (within 6-8 days) significantly increases serum IgE levels in unimmunized mice. In contrast, specific immunization regimens in non-alcohol consuming mice often require several weeks to obtain significant IgE levels. It is the robustness of this most polarized Th2 responses that affords us the opportunity to investigate the role of alcohol on Th2 mechanisms. The rapidity of increase in Serum IgE levels suggests that ethanol may rapidly up-regulate Th2 cytokines to stimulate B cells. The central hypothesis of the present exploratory/developmental proposal is that ethanol consumption promotes IgE responses through a Th2 cytokine burst. Three specific aims are proposed: 1) to determine whether Th2 cytokine/receptors are up-regulated, 2) to determine whether elevated IgE responses result from up-regulation of Th2 or down-regulation of Th1 cytokines, and 3) to determine the B cell source of IgE in alcohol-consuming mice. The experiments described represent an R21 exploratory/developmental proposal over a three-year time span. The proposed experiments are designed to help understand the underlying mechanisms of this most abused drug, alcohol, in polarizing the immune response toward Th2 function. [unreadable] [unreadable] [unreadable]